Temporal omics analysis in Syrian hamsters unravel cellular effector responses to moderate COVID-19

Nouailles, G.; Wyler, E.; Pennitz, P.; Postmus, D.; Vladimirova, D.; Kazmierski, J.; Pott, F.; Dietert, K.; Muelleder, M.; Farztdinov, V.; Obermayer, B.; Wienhold, S.M.; Andreotti, S.; Hoefler, T.; Sawitzki, B.; Drosten, C.; Sander, L.E.; Suttorp, N.; Ralser, M.; Beule, D.; Gruber, A.D.; Goffinet, C.; Landthaler, M.; Trimpert, J.; Witzenrath, M.

Temporal omics analysis in Syrian hamsters unravel cellular effector responses to moderate COVID-19

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Item Type:	Article
Title:	Temporal omics analysis in Syrian hamsters unravel cellular effector responses to moderate COVID-19
Creators Name:	Nouailles, G., Wyler, E., Pennitz, P., Postmus, D., Vladimirova, D., Kazmierski, J., Pott, F., Dietert, K., Muelleder, M., Farztdinov, V., Obermayer, B., Wienhold, S.M., Andreotti, S., Hoefler, T., Sawitzki, B., Drosten, C., Sander, L.E., Suttorp, N., Ralser, M., Beule, D., Gruber, A.D., Goffinet, C., Landthaler, M., Trimpert, J. and Witzenrath, M.
Abstract:	In COVID-19, immune responses are key in determining disease severity. However, cellular mechanisms at the onset of inflammatory lung injury in SARS-CoV-2 infection, particularly involving endothelial cells, remain ill-defined. Using Syrian hamsters as a model for moderate COVID-19, we conduct a detailed longitudinal analysis of systemic and pulmonary cellular responses, and corroborate it with datasets from COVID-19 patients. Monocyte-derived macrophages in lungs exert the earliest and strongest transcriptional response to infection, including induction of pro-inflammatory genes, while epithelial cells show weak alterations. Without evidence for productive infection, endothelial cells react, depending on cell subtypes, by strong and early expression of anti-viral, pro-inflammatory, and T cell recruiting genes. Recruitment of cytotoxic T cells as well as emergence of IgM antibodies precede viral clearance at day 5 post infection. Investigating SARS-CoV-2 infected Syrian hamsters thus identifies cell type-specific effector functions, providing detailed insights into pathomechanisms of COVID-19 and informing therapeutic strategies.
Keywords:	Alveolar Epithelial Cells, Animal Disease Models, COVID-19, Cytokines, Cytotoxic T-Lymphocytes, Endothelial Cells, Immunoglobulin M, Inflammation, Lung, Macrophages, Monocytes, SARS-CoV-2, Signal Transduction, Toll-Like Receptors, Animals, Cricetinae, Mesocricetus
Source:	Nature Communications
ISSN:	2041-1723
Publisher:	Nature Publishing Group
Volume:	12
Number:	1
Page Range:	4869
Date:	11 August 2021
Official Publication:	https://doi.org/10.1038/s41467-021-25030-7
PubMed:	View item in PubMed

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